Highly active antiretroviral therapy (HAART) is the cornerstone of treatment for Human Immunodeficiency Virus (HIV) infection. These treatments result in profound clinical improvement and prevent progression of disease. However, in order to be effective, the medication regimens must be rigorously adhered to over time. Studies by the investigative team and others have demonstrated clear associations between lower adherence and suboptimal treatment responses. Adherence research to date in HIV and other medical conditions suggests a variety of potential etiologies of poor adherence. Unfortunately, few interventions to improve adherence tested to date have been effective. The most promising interventions are flexible and multifactorial, targeting multiple potential barriers. We will conduct a randomized trial of a novel, pilot-tested, Social Cognitive Theory-based problem-solving derived adherence intervention, Managed Problem Solving (MAPS), in HIV infected individuals prescribed HAART. MAPS uses a 5-step process of problem orientation and definition, brainstorming for solutions to the identified barriers, selection and implementation of a plan of action, and assessment of implementation and feedback regarding its effectiveness. The intervention will address several potential adherence facilitators/barriers including linking medication taking with daily routines, medication reminders, refill reminders, and the involvement of social supports in medication taking in all subjects, and managing medication side effects, depression, substance abuse, competing demands, and psychoeducational barriers in a subset of subjects. Eligibility includes being equal to or >18 years of age and newly starting HAART or switching treatment due to lack of viral suppression. Two hundred subjects will be randomized 1:1 to the experimental or usual care groups. The experimental group will meet in person with an interventionist 4 times and by telephone 9 times over the first 3 months and then monthly by telephone for 9 months. Adherence will be monitored for both groups using microelectronic monitors (MEMS) and the intervention group will receive directed feedback on their adherence using these devices (virtual Directly Observed Therapy). The primary outcome will be adherence at 12 months and the secondary outcomes will be changes in viral load and CD4 counts at 12 months. If successful, this intervention will not only result in improved clinical outcomes in individuals who take part, but may also decrease the emergence of resistant HIV if incorporated into standard of care for HIV management.